The Eastern Virginia Medical School (EVMS) Biomarkers Developmental Laboratory (a member of the Early Detection Research Network or EDRN) is an integrated multidisciplinary program where investigators use mass spectrometry technology to mine the proteome for unique cancer biomarkers and protein expression fingerprints that can be used to improve the early detection of prostate, breast and head and neck cancers. As a member of the EDRN since its inception, EVMS has led significant efforts in the application of novel proteomic tools to examine the phenotypic traits of tumors and/or the tumor environment in search of protein biomarkers for the early detection and risk assessment of cancer. During the next five years, the EVMS team of investigators will continue to pursue the following aims independently and in collaboration with other network partners and industry-based scientists. The overall objectives will be met through three aims;1.) determine the clinical utility of protein profiling as a diagnostic test;2.) discover protein biomarkers for the early detection of cancer;and 3.) isolate and characterize protein biomarkers. In the first aim we will continue to develop SELDI profiling as a diagnostic tool for prostate and Head &Neck cancers. We also describe our studies to significantly improve this platform through improved peak picking and data analysis methods and we describe a novel proteomic tool, ClinProt UltraFlex (MALDI-TOF/TOF) for biomarker discovery. In the second aim we will examine body fluids and tissue for early markers of breast, prostate and H&N cancer. In the third aim we describe our approach to sequence identification and characterization of candidate biomarkers for early detection and risk assessment. Our unique team of investigators from basic sciences, mathematical sciences and the clinical arena supply the needed expertise to continue our work in biomarker development.